RL联合PTX对重度失血性休克大鼠肺缺血再灌注损伤的影响

Effect of sodium lactate ringer's injection combined with pentoxifylline on lung ischemia-reperfusion injury in rats with serious hemorrhagic shock

目的探讨乳酸钠林格液(RL)联合己酮可可碱(PTX)复苏对重度失血性休克大鼠肺缺血再灌注损伤的保护作用及机制。方法将48只健康雄性SD大鼠随机分为对照组、模型组、RL组及RL+PTX组各12只,后三组均采用改良Wigger's法制备重度失血性休克模型,模型制备成功后RL组予3倍失血量的RL复苏;RL+PTX组复苏方案同RL组,但复苏液中加入PTX;对照组仅行麻醉。分别于休克前、复苏前及复苏后1、2、4 h检测四组呼吸指数(RI);复苏后4 h检测肺通透指数、肺湿干质量比(W/D),观察肺组织病理学变化并进行肺损伤评分,测定肺组织中基质金属蛋白酶-2(MMP-2)和IL-8水平。结果与对照组比较,其余三组肺损伤评分、肺W/D、肺通透指数均显著升高,尤以RL组和RL+PTX组为著(P均<0.05);与RL组比较,RL/PTX组RI、肺通透指数、肺W/D显著降低,肺组织病理学变化显著减轻,肺损伤评分显著减少,肺组织MMP-2、IL-8水平显著降低(P均<0.05)。结论 RL联合PTX复苏可显著减轻重度失血性休克大鼠肺缺血再灌注损伤,可能机制为抑制肺组织内IL-8和MMP-2生成而减轻炎性反应。

Objective To explore the protective effect of sodium lactate ringer′s injection（RL） combined with pentoxifylline（PTX） on lung, ischemia-reperfusion injury in in rats with serious hemorrhagic shock. Methods A total of 48 healthy male SD rats were randomly divided into control group, model group, RL group and RL ＋ PTX group, 12 in each group. The serious hemorrhagic shock models were reproduced in the latter three groups by the modified Wigger′s method, then RL group was resuscitated with 3 x blood loss of RL. The same approach was applied to RL ＋ PTX group, and PTX was dissolved in RL solution. The control group was only anesthetized. Respiratory index （RI） was detected respectively in pre-shoek, pre-resuscitation, 1,2, 4 h after resuscitation ; At 4 h after resuscitation, the rats were sacrificed to measure the lung permeability index, lung wet dry weight ratio （ W/D）, the histological examination of lung and lung damage scores. The pulmonary concentrations of matrix metalloproteinase-2 （MMP-2）, IL-8 were determined in four groups. Results Compared with the control group, the lung damage score, the lung W/D, the lung permeability index were significandy increased in the other three groups, especially in the RL group and RL ＋ PTX group （ all P 〈 0.05 ） ; Compared with the RL group, R.I, the lung permeability index, the lung W/D, the lung injury score were significantly reduced, the lung histopathologieal change were significantly reduced, the pulmonary concentrations of MMP-2, IL-8 were lower in RL＋PTX group （ all P 〈 0.05 ）. Conclusion Resuscitation with RL ＋ PTX can significantly reduce lung ischemia-reperfusion injury in rats with serious hemorrhagic shock,the mechanism may be inhibiting the IL-8, MMP-2 generation of pulmonary to reduce inflammation response.